Extracellular Matrix Cues Regulate Mechanosensing and Mechanotransduction of Cancer Cells

Cells, Journal Year: 2024, Volume and Issue: 13(1), P. 96 - 96

Published: Jan. 2, 2024

Extracellular biophysical properties have particular implications for a wide spectrum of cellular behaviors and functions, including growth, motility, differentiation, apoptosis, gene expression, cell–matrix cell–cell adhesion, signal transduction mechanotransduction. Cells not only react to unambiguously mechanical cues from the extracellular matrix (ECM), but can occasionally manipulate features in parallel with biological characteristics, thus interfering downstream matrix-based both physiological pathological processes. Bidirectional interactions between cells (bio)materials vitro alter cell phenotype mechanotransduction, as well ECM structure, intentionally or unintentionally. Interactions mechanics vivo are importance variety diseases, primarily cancer. Stiffness values normal cancerous tissue range 500 Pa (soft) 48 kPa (stiff), respectively. Even shear flow increase 0.1–1 dyn/cm2 (normal tissue) 1–10 (cancerous tissue). There currently many new areas activity tumor research on various length scales, which highlighted this review. Moreover, complexity cancer is reduced common different tumors characteristics identify main pathways interaction. This all contributes standardization mechanotransduction models approaches, which, ultimately, increases understanding complex Finally, effects mechanics–biology pairing key insights clinical practice treatment and, consequently, translation.

Language: Английский

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Hybrid EMT Phenotype and Cell Membrane Tension Promote Colorectal Cancer Resistance to Ferroptosis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Abstract Intratumoral heterogeneity, including epithelial–mesenchymal transition (EMT), is one major cause of therapeutic resistance. The induction ferroptosis, an iron‐dependent death, has the potential in overcoming this resistance to traditional treatment modalities. However, roles distinct EMT phenotypes ferroptosis remain enigma. This study reports that 3D soft fibrin microenvironment confers colorectal cancer (CRC) cells hybrid phenotype and high level ferroptosis. activation histone acetylation WNT/β‐catenin signaling drives phenotypic transition, which promotes defense CRCs against via glutathione peroxidases/ferritin axis. Unexpectedly, E‐cadherin knockout but not 2D mediates integrin β 3 marked‐late state further enhances integrin‐mediated tension mitochondrial reprogramming. inhibition α v ‐mediated WNT/β‐catenin‐mediated sensitizes with without deficiency vivo, respectively. Further, patient‐derived tumoroids associated CRC In summary, uncovers previously unappreciated cell membrane only predict efficacy also potentiate development new ferroptosis‐based targeted strategies.

Language: Английский

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Mechanotransduction and epigenetic modulations of chromatin: Role of mechanical signals in gene regulation

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(3)

Published: Feb. 12, 2024

Abstract Mechanical forces may be generated within a cell due to tissue stiffness, cytoskeletal reorganization, and the changes (even subtle) in cell's physical surroundings. These of impose mechanical tension intracellular protein network (both cytosolic nuclear). could released by series protein–protein interactions often facilitated membrane lipids, lectins sugar molecules thus generate type signal drive cellular processes, including differentiation, polarity, growth, adhesion, movement, survival. Recent experimental data have accentuated molecular mechanism this transduction pathway, dubbed mechanotransduction. Mechanosensitive proteins plasma discern channel information interior. Cells respond message altering their arrangement directly transmitting nucleus through connection cytoskeleton nucleoskeleton before despatched biochemical signaling pathways. Nuclear transmission force leads activation chromatin modifiers modulation epigenetic landscape, inducing reorganization gene expression regulation; time chemical messengers (transcription factors) arrive into nucleus. While significant research has been done on role mechanotransduction tumor development cancer progression/metastasis, mechanistic basis force‐activated carcinogenesis is still enigmatic. Here, review, we discussed various cues connections better comprehend also explored detailed some multiple players (proteins macromolecular complexes) involved Thus, described an avenue: how stress directs modulate epigenome cells aberrant phenotype.

Language: Английский

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The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2135 - 2135

Published: Feb. 10, 2024

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing formation cancerous tissues. CI can be further categorized into two distinct yet interrelated components: locomotion (CIL) and proliferation (CIP). These components have historically been viewed as separate processes, but emerging research suggests that they may regulated by both shared pathways. Specifically, recent studies indicated CIP CIL utilize mechanotransduction pathways, process involves cells sensing responding to mechanical forces. This review article describes role in CI, shedding light on how forces regulate CIP. Emphasis is placed filamin A (FLNA)-mediated mechanotransduction, elucidating FLNA senses translates them biochemical signals cell proliferation. In addition FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable directly indirectly binding specific DNA sequences distant genes gene expression, emerge sensitive players signaling pathways CI. presents methods identifying these TAF profiling associated changes chromatin structure, offering valuable insights other biological functions mediated mechanotransduction. Finally, it addresses unanswered questions fields delineates their possible future directions.

Language: Английский

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Coordinated in confined migration: crosstalk between the nucleus and ion channel-mediated mechanosensation

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: 34(10), P. 809 - 825

Published: Jan. 29, 2024

Language: Английский

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Chromatin plasticity in mechanotransduction

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 88, P. 102376 - 102376

Published: May 28, 2024

Living organisms can detect and respond to physical forces at the cellular level. The pathways that transmit these nucleus allow cells react quickly consistently environmental changes. Mechanobiology involves interaction between biological processes is crucial for driving embryonic development adapting cues during adulthood. Molecular studies have shown sense mechanical signals directly through membrane receptors linked cytoskeleton or indirectly biochemical cascades influence gene expression adaptation. This review will explore role of epigenetic modifications, emphasizing 3D genome architecture nuclear structures as responders stimuli, which ensure memory adaptability. Understanding how are transduced regulate cell functioning, governing such programming reprogramming, essential advancing our knowledge human diseases.

Language: Английский

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Leveraging computational modeling to explore epithelial and endothelial cell monolayer mechanobiology

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Peripheral heterochromatin tethering is required for chromatin-based nuclear mechanical response

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 16, 2025

The cell nucleus is a mechanically responsive structure that governs how external forces affect chromosomes. Chromatin, particularly transcriptionally inactive heterochromatin, resists nuclear deformations through its mechanical response. However, chromatin also exhibits liquid-like properties, casting ambiguity on the physical mechanisms of chromatin-based elasticity. To determine heterochromatin strengthens response, we performed polymer physics simulations model validated by micromechanical measurements and chromosome conformation capture data. attachment peripheral to lamina required transmit directly elicit elastic Thus, increases in levels increase rigidity increasing linkages between lamina. Crosslinks within such as HP1 α proteins, can stiffen nuclei, but only if peripherally tethered. In contrast, affinity interactions may drive liquid-liquid phase separation do not contribute rigidity. When stretched, gel-like bear stresses deform, while more fluid-like interior euchromatin less perturbed. heterochromatin's internal stiffness regulate mechanics via lamina, enabling mechanosensing measurement nucleus' architecture.

Language: Английский

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Nuclear mechano-confinement induces geometry-dependent HP1α condensate alterations

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 25, 2025

Abstract Cells sense external physical cues through complex processes involving signaling pathways, cytoskeletal dynamics, and transcriptional regulation to coordinate a cellular response. A key emerging principle underlying such mechanoresponses is the interplay between nuclear morphology, chromatin organization, dynamic behavior of bodies as HP1α condensates. Here, applying Airyscan super-resolution live cell imaging, we report hitherto undescribed level mechanoresponse triggered by confinement below their resting diameter, which elicits changes in number, size dynamics Utilizing biophysical polymer models, observe radial redistribution condensates within nucleus, influenced geometry. These insights shed new light on relationship forces shape organization mechanoreception.

Language: Английский

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Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169044 - 169044

Published: Feb. 1, 2025

Language: Английский

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